The personal care industry is focused on developing safe, more efficacious, and increasingly milder products, that are routinely undergoing preclinical and clinical testing before becoming available for consumer use on skin. In vitro systems based on skin reconstructed equivalents are now established for the preclinical assessment of product irritation potential and as alternative testing methods to the classic Draize rabbit skin irritation test. We have used the 3-D EpiDerm™ model system to evaluate tissue viability and primary cytokine interleukin-1α release as a way to evaluate the potential dermal irritation of 224 non-ionic, amphoteric and/or anionic surfactant-containing formulations, or individual raw materials. As part of our testing programme, two representative benchmark materials with known clinical skin irritation potential were qualified through repeated testing, for use as references for the skin irritation evaluation of formulations containing new surfactant ingredients. We have established a correlation between the in vitro screening approach and clinical testing, and are continually expanding our database to enhance this correlation. This testing programme integrates the efforts of global manufacturers of personal care products that focus on the development of increasingly milder formulations to be applied to the skin, without the use of animal testing.

Nanotechnology is one of the most important technological developments of the 21st century. In silico methods to predict toxicity, such as quantitative structure–activity relationships (QSARs), promote the safe-by-design approach for the development of new materials, including nanomaterials. In this study, a set of cytotoxicity experimental data corresponding to 19 data points for silica nanomaterials were
investigated, to compare the widely employed CORAL and Random Forest approaches in terms of their usefulness for developing so-called ‘nano-QSAR’ models. ‘External’ leave-one-out cross-validation (LOO) analysis was performed, to validate the two different approaches. An analysis of variable importance measures and signed feature contributions for both algorithms was undertaken, in order to interpret the models developed. CORAL showed a more pronounced difference between the average coefficient of determination (R2) for training and for LOO (0.83 and 0.65 for training and LOO, respectively), compared to Random Forest (0.87 and 0.78 without bootstrap sampling, 0.90 and 0.78 with bootstrap sampling), which may be due to overfitting. With regard to the physicochemical properties of the nanomaterials, the aspect ratio and zeta potential were found to be the two most important variables for Random Forest, and the average feature contributions calculated for the corresponding descriptors were consistent with the clear trends observed in the data set: less negative zeta potential values and lower aspect ratio values were associated with higher cytotoxicity. In contrast, CORAL failed to capture these trends.

Some of the advantages of retina organ culture models include their efficient and easy handling and the ability to standardise relevant parameters. Additionally, when porcine eyes are obtained from the food industry, no animals are killed solely for research purposes. To induce retinal degeneration, a commonly used toxic substance, N-methyl-D-aspartate (NMDA), was applied to the cultures. To this end, organotypic cultures of porcine retinas were cultured and treated with different doses of NMDA (0 [control], 50, 100 and 200μM) on day 2 for 48 hours. On day 7, the retinas were cryo-conserved for histological, Western blot and quantitative rt-PCR (qrt-PCR) analyses. NMDA treatment was found to significantly increase retinal ganglion cell (RGC) apoptosis in all the treated groups, without a profound RGC loss. In addition, the intrinsic apoptotic pathway was activated in the 50μM and 100μM NMDA groups, whereas induced nitric oxide synthase (iNOS) expression was increased in the 200μM group. A slight microglial response was detectable, especially in the 100μM group. NMDA treatment induced apoptosis, oxidative stress and a slight microglia activation. All these effects mimic a chronic slow progressive disease that especially affects RGCs, such as glaucoma. A particular advantage of this model is that mediators that can interact in the very early stages of the onset of RGC death, can be easily detected and potential therapies can be tested.

The Annual Statistics of Scientific Procedures on Living Animals Great Britain 2015 indicate that the Home Office were correct in recommending that caution should be exercised when interpreting the 2014 data as an apparent decline in animal experiments. The 2015 report shows that, as the changes to the format of the annual statistics have become more familiar and less problematic, there has been a re-emergence of the upward trend in animal research and testing in Great Britain. The 2015 statistics report an increase in animal procedures (up to 4,142,631) and in the number of animals used (up to 4,069,349). This represents 1% more than the totals in 2013, and a 7% increase on the procedures reported in 2014. This paper details an analysis of these most recent statistics, providing information on overall animal use and highlighting specific issues associated with genetically-altered animals, dogs and primates. It also reflects on areas of the new format that have previously been highlighted as being problematic, and concludes with a discussion about the use of animals in regulatory research and testing, and how there are significant missed opportunities for replacing some of the animal-based tests in this area.

Kristie Sullivan

Efforts toward replacing the use of animals in toxicology testing have begun to make significant headway in the last several years, due to co-operative and pragmatic efforts on the part of many stakeholders, and the public pressure that non-governmental advocacy organisations represent. Science-focused advocacy organisations have a unique role to play in these efforts, as they often have flexibility to adapt quickly to keep a project going and forge connections among different kinds of stakeholders to help encourage buy-in. This year, meaningful progress has been made, especially in regulatory laws and policies, which will lead to the replacement of animals in toxicology testing. In order to keep this momentum, we need to measure progress — but this requires improved transparency and regular reporting of animal use. In addition, we should consider how strategies that have successfully reduced and replaced animal use in toxicology can be applied to basic biomedical research practices.

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ATLA is published by FRAME, and has been a key scientific journal in the field of laboratory animal alternatives for more than 30 years.
Circulated worldwide, ATLA is distributed to individuals, organisations and institutions. It covers the latest research relating to alternatives to the use of laboratory animals.